BG106257A - Нафтиридинови производни, методи за получаването им, използването им и фармацевтични състави, коитоги съдържат - Google Patents

Нафтиридинови производни, методи за получаването им, използването им и фармацевтични състави, коитоги съдържат Download PDF

Info

Publication number: BG106257A
Authority: BG; Bulgaria
Prior art keywords: alkyl; aryl; heteroaryl; zero; cycloalkyl
Prior art date: 1999-07-02

Application number

BG106257A

Other languages

Bulgarian (bg)

English (en)

Inventor

Anuschirvan Peyman

Karl-Heinz Scheunemann

Thomas Gadek

Jean-Francois Gourvest

Jean-Marie Ruxer

Original Assignee

Aventis Pharma Deutschland Gmbh

Genentech, Inc.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-07-02

Filing date

2001-12-20

Publication date

2002-10-31

2001-12-20 Application filed by Aventis Pharma Deutschland Gmbh, Genentech, Inc. filed Critical Aventis Pharma Deutschland Gmbh

2002-10-31 Publication of BG106257A publication Critical patent/BG106257A/bg

Links

238000000034 method Methods 0.000 title claims abstract description 44
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
230000008569 process Effects 0.000 title abstract description 13
238000002360 preparation method Methods 0.000 title abstract description 11
150000001875 compounds Chemical class 0.000 claims abstract description 199
150000003839 salts Chemical class 0.000 claims abstract description 57
239000000651 prodrug Substances 0.000 claims abstract description 52
229940002612 prodrug Drugs 0.000 claims abstract description 52
102100022337 Integrin alpha-V Human genes 0.000 claims abstract description 32
108010048673 Vitronectin Receptors Proteins 0.000 claims abstract description 28
208000006386 Bone Resorption Diseases 0.000 claims abstract description 18
230000024279 bone resorption Effects 0.000 claims abstract description 18
239000003112 inhibitor Substances 0.000 claims abstract description 15
208000001132 Osteoporosis Diseases 0.000 claims abstract description 13
238000011321 prophylaxis Methods 0.000 claims abstract description 11
239000002464 receptor antagonist Substances 0.000 claims abstract description 5
229940044551 receptor antagonist Drugs 0.000 claims abstract description 5
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 131
239000001257 hydrogen Substances 0.000 claims description 89
229910052739 hydrogen Inorganic materials 0.000 claims description 89
-1 nitro, hydroxycarbonyl Chemical group 0.000 claims description 73
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 52
239000000460 chlorine Substances 0.000 claims description 51
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 49
229910052801 chlorine Inorganic materials 0.000 claims description 49
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 48
125000003118 aryl group Chemical group 0.000 claims description 46
125000000217 alkyl group Chemical group 0.000 claims description 43
239000011737 fluorine Substances 0.000 claims description 43
229910052731 fluorine Inorganic materials 0.000 claims description 43
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 42
125000004093 cyano group Chemical group *C#N 0.000 claims description 38
125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 37
125000001424 substituent group Chemical group 0.000 claims description 37
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
239000000203 mixture Substances 0.000 claims description 35
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 31
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 31
229910052794 bromium Inorganic materials 0.000 claims description 31
150000002431 hydrogen Chemical group 0.000 claims description 29
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
125000001072 heteroaryl group Chemical group 0.000 claims description 27
125000000753 cycloalkyl group Chemical group 0.000 claims description 26
125000005842 heteroatom Chemical group 0.000 claims description 26
229910052757 nitrogen Inorganic materials 0.000 claims description 24
238000011282 treatment Methods 0.000 claims description 24
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 22
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 20
229910052760 oxygen Inorganic materials 0.000 claims description 20
239000001301 oxygen Chemical group 0.000 claims description 20
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
229910052717 sulfur Chemical group 0.000 claims description 19
239000011593 sulfur Chemical group 0.000 claims description 19
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 16
125000004432 carbon atom Chemical group C* 0.000 claims description 16
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
125000000524 functional group Chemical group 0.000 claims description 14
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 13
239000002243 precursor Substances 0.000 claims description 13
125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 12
206010028980 Neoplasm Diseases 0.000 claims description 12
229910052740 iodine Inorganic materials 0.000 claims description 12
125000000732 arylene group Chemical group 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
229920006395 saturated elastomer Polymers 0.000 claims description 9
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 8
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 8
SCNPUDCZXNUNQZ-UHFFFAOYSA-N 4-(furan-2-yl)-1-[(4-methoxyphenyl)methyl]pyrazolo[3,4-d]pyrimidine Chemical group C1=CC(OC)=CC=C1CN1C2=NC=NC(C=3OC=CC=3)=C2C=N1 SCNPUDCZXNUNQZ-UHFFFAOYSA-N 0.000 claims description 8
125000006702 (C1-C18) alkyl group Chemical group 0.000 claims description 7
150000001450 anions Chemical class 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
230000002265 prevention Effects 0.000 claims description 7
125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 6
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 6
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 5
206010027476 Metastases Diseases 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 4
125000000539 amino acid group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
208000037803 restenosis Diseases 0.000 claims description 4
230000004614 tumor growth Effects 0.000 claims description 4
201000001320 Atherosclerosis Diseases 0.000 claims description 3
208000024172 Cardiovascular disease Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 2
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
239000002260 anti-inflammatory agent Substances 0.000 claims description 2
125000001769 aryl amino group Chemical group 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 12
125000004657 aryl sulfonyl amino group Chemical group 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
208000017169 kidney disease Diseases 0.000 claims 1
210000004027 cell Anatomy 0.000 abstract description 28
210000002997 osteoclast Anatomy 0.000 abstract description 16
230000003993 interaction Effects 0.000 abstract description 13
239000004480 active ingredient Substances 0.000 abstract description 9
230000033115 angiogenesis Effects 0.000 abstract description 6
239000003814 drug Substances 0.000 abstract description 5
239000003446 ligand Substances 0.000 abstract description 4
238000002560 therapeutic procedure Methods 0.000 abstract description 4
230000021164 cell adhesion Effects 0.000 abstract description 3
230000002401 inhibitory effect Effects 0.000 abstract description 3
230000008611 intercellular interaction Effects 0.000 abstract description 2
230000008619 cell matrix interaction Effects 0.000 abstract 1
230000035755 proliferation Effects 0.000 abstract 1
230000002792 vascular Effects 0.000 abstract 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
125000004435 hydrogen atom Chemical group [H]* 0.000 description 19
239000000243 solution Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
125000006239 protecting group Chemical group 0.000 description 14
239000002904 solvent Substances 0.000 description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
238000012360 testing method Methods 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
210000000988 bone and bone Anatomy 0.000 description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
239000000969 carrier Substances 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 9
101000803709 Homo sapiens Vitronectin Proteins 0.000 description 8
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
239000005557 antagonist Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
102000007399 Nuclear hormone receptor Human genes 0.000 description 7
108020005497 Nuclear hormone receptor Proteins 0.000 description 7
235000001014 amino acid Nutrition 0.000 description 7
229940024606 amino acid Drugs 0.000 description 7
150000001413 amino acids Chemical class 0.000 description 7
125000003277 amino group Chemical group 0.000 description 7
125000002619 bicyclic group Chemical group 0.000 description 7
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
239000002953 phosphate buffered saline Substances 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical group C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 description 6
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
208000020084 Bone disease Diseases 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
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ZTYNVDHJNRIRLL-FWZKYCSMSA-N rhodostomin Chemical compound C([C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H]2C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CSSC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CC=2NC=NC=2)C(O)=O)[C@@H](C)O)=O)CSSC[C@H]2C(=O)N[C@H]3CSSC[C@@H](C(NCC(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H]2NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)CN)CSSC2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(N4)=O)CSSC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC3=O)C(=O)N[C@@H](CCCCN)C(=O)N1)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=CC=C1 ZTYNVDHJNRIRLL-FWZKYCSMSA-N 0.000 description 6
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239000003085 diluting agent Substances 0.000 description 5
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
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125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
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125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
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MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
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239000007922 nasal spray Substances 0.000 description 1
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239000012299 nitrogen atmosphere Substances 0.000 description 1
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BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
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OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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239000000546 pharmaceutical excipient Substances 0.000 description 1
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230000000144 pharmacologic effect Effects 0.000 description 1
150000002993 phenylalanine derivatives Chemical class 0.000 description 1
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230000004962 physiological condition Effects 0.000 description 1
210000002826 placenta Anatomy 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
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239000000186 progesterone Substances 0.000 description 1
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229960002429 proline Drugs 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
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239000003998 snake venom Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
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239000012312 sodium hydride Substances 0.000 description 1
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125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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GHKYODAPFJWTTK-VWLOTQADSA-N tert-butyl (2s)-2-(benzenesulfonamido)-3-[6-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)piperidin-1-yl]purin-9-yl]propanoate Chemical compound N([C@@H](CN1C2=NC=NC(=C2N=C1)N1CCC(CC1)C=1N=C2NCCCC2=CC=1)C(=O)OC(C)(C)C)S(=O)(=O)C1=CC=CC=C1 GHKYODAPFJWTTK-VWLOTQADSA-N 0.000 description 1
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JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 1
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CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
230000008354 tissue degradation Effects 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
PCFIPYFVXDCWBW-UHFFFAOYSA-N tricyclo[3.3.1.03,7]nonane Chemical compound C1C(C2)C3CC2CC1C3 PCFIPYFVXDCWBW-UHFFFAOYSA-N 0.000 description 1
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210000004881 tumor cell Anatomy 0.000 description 1
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JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
210000003556 vascular endothelial cell Anatomy 0.000 description 1
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235000019166 vitamin D Nutrition 0.000 description 1
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125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Dermatology (AREA)
Pain & Pain Management (AREA)
Ophthalmology & Optometry (AREA)
Immunology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

BG106257A 1999-07-02 2001-12-20 Нафтиридинови производни, методи за получаването им, използването им и фармацевтични състави, коитоги съдържат BG106257A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP99112636A EP1065207A1 (de)	1999-07-02	1999-07-02	Naphthyridin derivate, Verfahren zu ihrer Herstellung, ihre Anwendung und sie enthaltende pharmazeutische Zusammenfassungen
PCT/EP2000/005920 WO2001002398A1 (en)	1999-07-02	2000-06-26	Naphthyridine derivatives, processes for their preparation, their use and pharmaceutical compositions comprising them

Publications (1)

Publication Number	Publication Date
BG106257A true BG106257A (bg)	2002-10-31

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BG106257A BG106257A (bg)	1999-07-02	2001-12-20	Нафтиридинови производни, методи за получаването им, използването им и фармацевтични състави, коитоги съдържат

Country Status (33)

Country	Link
US (2)	US6743800B1 (de)
EP (2)	EP1065207A1 (de)
JP (1)	JP2003503496A (de)
KR (1)	KR20020015996A (de)
CN (1)	CN1160356C (de)
AR (1)	AR024622A1 (de)
AT (1)	ATE305471T1 (de)
AU (1)	AU775386B2 (de)
BG (1)	BG106257A (de)
BR (1)	BR0012129A (de)
CA (1)	CA2376668C (de)
CZ (1)	CZ20014605A3 (de)
DE (2)	DE60022890T4 (de)
DK (1)	DK1210348T3 (de)
EA (1)	EA004369B1 (de)
EE (1)	EE200100711A (de)
ES (1)	ES2250157T3 (de)
HK (1)	HK1050003B (de)
HR (1)	HRP20010946A2 (de)
HU (1)	HUP0203539A3 (de)
IL (1)	IL147248A0 (de)
MX (1)	MXPA01013435A (de)
MY (1)	MY133246A (de)
NO (1)	NO20016404L (de)
NZ (1)	NZ516058A (de)
PL (1)	PL352280A1 (de)
SK (1)	SK19132001A3 (de)
TR (1)	TR200103856T2 (de)
TW (1)	TW593319B (de)
UA (1)	UA73133C2 (de)
WO (1)	WO2001002398A1 (de)
YU (1)	YU92201A (de)
ZA (1)	ZA200200016B (de)

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DE10042655A1 (de) *	2000-08-31	2002-03-14	Aventis Pharma Gmbh	Verfahren zur Herstellung von Inhibitoren der Zell-Adhäsion
FR2847254B1 (fr)	2002-11-19	2005-01-28	Aventis Pharma Sa	Nouveaux derives antagonistes du recepteur de la vitronectine, leur procede de preparation, leur application comme medicaments et les compositions pharmaceutiques les refermant
US7632950B2 (en) *	2003-08-18	2009-12-15	Fujifilm Finechemicals Co., Ltd	Pyridyltetrahydropyridines and pyridylpiperidines and method of manufacturing them
FR2870541B1 (fr) *	2004-05-18	2006-07-14	Proskelia Sas	Derives de pyrimidines antigonistes du recepteur de la vitronectine
US20110237605A1 (en)	2010-03-26	2011-09-29	Eric Phillips	Molecular Crystal of (4-(1,8-Naphthyridin-2-YL)Piperidin-1-YL)Pyrimidine Derivative
CN103665043B (zh)	2012-08-30	2017-11-10	江苏豪森药业集团有限公司	一种替诺福韦前药及其在医药上的应用
EP3050878B1 (de)	2013-09-24	2021-10-27	FUJIFILM Corporation	Neuartige stickstoffhaltige verbindung oder salz davon oder metallkomplex davon
WO2020097400A1 (en)	2018-11-07	2020-05-14	Dana-Farber Cancer Institute, Inc.	Imidazopyridine derivatives and aza-imidazopyridine derivatives as janus kinase 2 inhibitors and uses thereof
EP3876939A4 (de)	2018-11-07	2022-08-10	Dana-Farber Cancer Institute, Inc.	Benzothiazolderivate und 7-aza-benzothiazol-derivate als inhibitoren der janus-kinase-2 und verwendungen davon
EP3876930A4 (de)	2018-11-07	2022-07-20	Dana-Farber Cancer Institute, Inc.	Benzimidazolderivate und aza-benzimidazol-derivate als inhibitoren der janus-kinase 2 und verwendungen davon
BR112022022409A2 (pt)	2020-05-06	2023-02-07	Ajax Therapeutics Inc	6-heteroarilóxi benzimidazóis e azabenzimidazóis como inibidores de jak2
WO2022140527A1 (en)	2020-12-23	2022-06-30	Ajax Therapeutics, Inc.	6-heteroaryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors
CA3234638A1 (en)	2021-11-09	2023-05-19	Ajax Therapeutics, Inc.	6-heteroaryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors
WO2023086320A1 (en)	2021-11-09	2023-05-19	Ajax Therapeutics, Inc.	Forms and compositions of inhibitors of jak2
US12600722B2 (en)	2022-07-18	2026-04-14	Incyte Corporation	Tetracyclic compounds as DGK inhibitors
US12600723B2 (en)	2022-07-18	2026-04-14	Incyte Corporation	Tetracyclic compounds as DGK inhibitors

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AU3938997A (en)	1996-08-26	1998-03-19	Novo Nordisk A/S	A novel endoglucanase
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EP0946164A4 (de) *	1996-10-30	2000-08-23	Merck & Co Inc	Integrin antagonisten
DE19653646A1 (de) *	1996-12-20	1998-06-25	Hoechst Ag	Substituierte Purinderivate, Verfahren zu deren Herstellung, sie enthaltende Mittel und deren Verwendung
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EP0933367A1 (de) *	1997-12-19	1999-08-04	Hoechst Marion Roussel Deutschland GmbH	Acylguanidin Derivate als Inhibitoren von Knochenaufsauge und als Vitronectin Rezeptor Antagonisten
JP2002501054A (ja) *	1998-01-23	2002-01-15	アヴェンティスファルマドイチェラントゲーエムベーハー	骨吸収の阻害剤として及び細胞接着の阻害剤としての新規のスルホンアミド誘導体
PA8474101A1 (es) *	1998-06-19	2000-09-29	Pfizer Prod Inc	Compuestos de pirrolo [2,3-d] pirimidina
US6365589B1 (en) *	1998-07-02	2002-04-02	Bristol-Myers Squibb Pharma Company	Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists
EP1065207A1 (de) *	1999-07-02	2001-01-03	Aventis Pharma Deutschland GmbH	Naphthyridin derivate, Verfahren zu ihrer Herstellung, ihre Anwendung und sie enthaltende pharmazeutische Zusammenfassungen
DE10042655A1 (de) *	2000-08-31	2002-03-14	Aventis Pharma Gmbh	Verfahren zur Herstellung von Inhibitoren der Zell-Adhäsion
WO2003059289A2 (en) *	2002-01-10	2003-07-24	Neurogen Corporation	Melanin concentrating hormone receptor ligands: substituted benzoimidazole analogues
JP2008047614A (ja)	2006-08-11	2008-02-28	Showa Shell Sekiyu Kk	吸着材を利用した改良型太陽電池モジュール

1999
- 1999-07-02 EP EP99112636A patent/EP1065207A1/de not_active Withdrawn
2000
- 2000-06-26 HU HU0203539A patent/HUP0203539A3/hu unknown
- 2000-06-26 YU YU92201A patent/YU92201A/sh unknown
- 2000-06-26 DE DE60022890T patent/DE60022890T4/de not_active Expired - Lifetime
- 2000-06-26 IL IL14724800A patent/IL147248A0/xx unknown
- 2000-06-26 CN CNB008123365A patent/CN1160356C/zh not_active Expired - Fee Related
- 2000-06-26 CZ CZ20014605A patent/CZ20014605A3/cs unknown
- 2000-06-26 HR HR20010946A patent/HRP20010946A2/hr not_active Application Discontinuation
- 2000-06-26 DE DE60022890A patent/DE60022890D1/de not_active Expired - Fee Related
- 2000-06-26 NZ NZ516058A patent/NZ516058A/xx unknown
- 2000-06-26 US US10/030,301 patent/US6743800B1/en not_active Expired - Fee Related
- 2000-06-26 BR BR0012129-0A patent/BR0012129A/pt not_active IP Right Cessation
- 2000-06-26 SK SK1913-2001A patent/SK19132001A3/sk unknown
- 2000-06-26 AU AU59787/00A patent/AU775386B2/en not_active Ceased
- 2000-06-26 DK DK00945825T patent/DK1210348T3/da active
- 2000-06-26 ES ES00945825T patent/ES2250157T3/es not_active Expired - Lifetime
- 2000-06-26 PL PL00352280A patent/PL352280A1/xx not_active Application Discontinuation
- 2000-06-26 CA CA002376668A patent/CA2376668C/en not_active Expired - Fee Related
- 2000-06-26 AT AT00945825T patent/ATE305471T1/de not_active IP Right Cessation
- 2000-06-26 KR KR1020017016961A patent/KR20020015996A/ko not_active Ceased
- 2000-06-26 EA EA200200122A patent/EA004369B1/ru not_active IP Right Cessation
- 2000-06-26 HK HK03102163.4A patent/HK1050003B/zh not_active IP Right Cessation
- 2000-06-26 UA UA2002020852A patent/UA73133C2/uk unknown
- 2000-06-26 JP JP2001507835A patent/JP2003503496A/ja not_active Withdrawn
- 2000-06-26 MX MXPA01013435A patent/MXPA01013435A/es active IP Right Grant
- 2000-06-26 EE EEP200100711A patent/EE200100711A/xx unknown
- 2000-06-26 WO PCT/EP2000/005920 patent/WO2001002398A1/en not_active Ceased
- 2000-06-26 EP EP00945825A patent/EP1210348B9/de not_active Expired - Lifetime
- 2000-06-26 TR TR2001/03856T patent/TR200103856T2/xx unknown
- 2000-06-29 AR ARP000103313A patent/AR024622A1/es active IP Right Grant
- 2000-06-29 MY MYPI20002962 patent/MY133246A/en unknown
- 2000-09-01 TW TW089117925A patent/TW593319B/zh not_active IP Right Cessation
2001
- 2001-12-20 BG BG106257A patent/BG106257A/bg unknown
- 2001-12-28 NO NO20016404A patent/NO20016404L/no not_active Application Discontinuation
2002
- 2002-01-02 ZA ZA200200016A patent/ZA200200016B/en unknown
2004
- 2004-03-24 US US10/808,496 patent/US20040198718A1/en not_active Abandoned

Also Published As

Publication number	Publication date
TW593319B (en)	2004-06-21
JP2003503496A (ja)	2003-01-28
CA2376668C (en)	2007-01-02
IL147248A0 (en)	2002-08-14
TR200103856T2 (tr)	2002-06-21
ZA200200016B (en)	2003-01-02
EP1065207A1 (de)	2001-01-03
HK1050003B (zh)	2005-04-29
NO20016404D0 (no)	2001-12-28
NO20016404L (no)	2002-03-01
BR0012129A (pt)	2002-05-07
WO2001002398A1 (en)	2001-01-11
UA73133C2 (en)	2005-06-15
MXPA01013435A (es)	2002-07-22
KR20020015996A (ko)	2002-03-02
HK1050003A1 (en)	2003-06-06
CN1372559A (zh)	2002-10-02
DK1210348T3 (da)	2006-01-16
ATE305471T1 (de)	2005-10-15
AR024622A1 (es)	2002-10-16
CA2376668A1 (en)	2001-01-11
EP1210348A1 (de)	2002-06-05
AU775386B2 (en)	2004-07-29
CN1160356C (zh)	2004-08-04
EA200200122A1 (ru)	2002-06-27
MY133246A (en)	2007-10-31
HUP0203539A2 (hu)	2003-02-28
DE60022890T4 (de)	2007-03-29
US6743800B1 (en)	2004-06-01
DE60022890T2 (de)	2006-06-29
EA004369B1 (ru)	2004-04-29
YU92201A (sh)	2004-07-15
SK19132001A3 (sk)	2002-07-02
EE200100711A (et)	2003-04-15
EP1210348B1 (de)	2005-09-28
US20040198718A1 (en)	2004-10-07
DE60022890D1 (de)	2006-02-09
CZ20014605A3 (cs)	2002-06-12
PL352280A1 (en)	2003-08-11
AU5978700A (en)	2001-01-22
HRP20010946A2 (en)	2003-02-28
ES2250157T3 (es)	2006-04-16
NZ516058A (en)	2003-01-31
HUP0203539A3 (en)	2005-01-28
EP1210348B9 (de)	2006-04-26

Publication	Publication Date	Title
CA2376668C (en)	2007-01-02	Naphthyridine derivatives, processes for their preparation, their use and pharmaceutical compositions comprising them
JPH10182645A (ja)	1998-07-07	置換プリン誘導体、その製法、その使用およびそれを含有する組成物
US6747016B1 (en)	2004-06-08	Substituted purine derivatives as inhibitors of cell adhesion
US7259159B2 (en)	2007-08-21	Guanidino derivatives as inhibitors of cell adhesion